The technology of oral fluid testing for drugs of abuse has been advancing, but urinalysis remains the standard matrix for drug screening in most settings, including methadone maintenance and other outpatient addiction treatment, despite major practical advantages of oral fluid over urine specimen collection. These are specifically the elimination of privacy issues (and increase in patient dignity), the need for a dedicated bathroom, the need for a same-gender observer (if observation is done), no effects of ?shy bladder?, and the near elimination of potential adulteration of specimens, the latter requiring numerous validity tests to detect for urine. Recent research indicates that with the use of state of art techniques (liquid chromatography with tandem mass spectrometry- LC/MS/MS), the overall window of detection has become similar for oral fluid and urine. Despite these advantages, oral fluid is still not widely used in methadone treatment, other outpatient addiction treatment, and other settings such as probation/parole programs, drug courts, safety-sensitive workplaces, and child protective services, that need to monitor the drug use of their clients or employees. In addition, there is great potential for using oral fluid in drug epidemiological studies, such as household surveys and ?street studies,? where urinalysis is largely impractical, but where timely drug surveillance is critical for early detection of and changes in local and national drug epidemics. In particular, expansion of oral fluid drug testing would contribute to ?real time surveillance of the opioid crisis? (President?s Commission, 2017), including better monitoring of the abuse of powerful synthetic opioids (e.g., fentanyl, oxycodone). One important barrier to the wider use of oral fluid is a paucity of contemporary data comparing the results of oral fluid analysis to urinalysis, the current standard, for large samples of paired specimens provided by the same individuals at the same time. Consequently, the specific aims of this application are: 1. Identify differences (if any) between oral fluid analysis and urinalysis in the detection of different major drug classes and the most common drug compounds within a set of 123 possible compounds, including recent ?designer drugs.? The study will compare the results between state-of-the-art oral fluid testing and urinalysis for new patients admitted to methadone maintenance treatment nationally (n = 1,000), selected for regional diversity. 2. Determine the utility of oral fluid and urine drug screening by LC/MS/MS-only as compared with standard immunoassay screening followed by LC/MS/MS confirmation of positives only. 3. Determine the sensitivity of oral fluid analysis and urinalysis as compared with self-reports of recent drug use obtained at admission to methadone treatment. If oral fluid analysis yields results at least equivalent to accepted standard urinalysis, then the use of oral fluid both in addiction treatment and other settings where urinalysis is commonly used today, and settings where any matrix other than oral fluid is impractical (e.g., most epidemiological research), would be highly supported.